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. Author manuscript; available in PMC: 2022 Feb 1.
Published in final edited form as: J Diabetes Complications. 2020 Sep 16;35(2):107734. doi: 10.1016/j.jdiacomp.2020.107734

Figure 2: Ceramides and Insulin Resistance.

Figure 2:

Ceramide plays a central role in insulin resistance and β-cell death. Obesity and hyperglycemia both increase circulating shorter-chain saturated free fatty acids (FFA) that serve as substrates for and induce de novo ceramide synthesis24, 25. Chronic inflammation in obesity is associated with TLR4 activation, which in turn increases cytokines and ceramide levels189. Diabetes is associated with decreased adiponectin, which is a known inhibitor of ceramide synthesis164. Ceramide activates PP2A and PKCζ, which inhibit AKT/PKB and decrease insulin sensitivity58, 59. Ceramide also activates pro-inflammatory and pro-apoptotic pathways via caspase, PP1, PKc, and cathepsin D15, 57, leading to pancreatic β-cell death53.